- ICH GCP
- US-Register für klinische Studien
- Klinische Studie NCT01487993
Metformin in Obese Children and Adolescents (MetVoorMin)
An Efficacy, Safety and Pharmacokinetic Study on the Short-term and Long-term Use of Metformin in Obese Children and Adolescents
Studienübersicht
Status
Bedingungen
Intervention / Behandlung
Detaillierte Beschreibung
The prevalence of obesity in children and adolescents is increasing rapidly and is associated with significant medical and psychosocial consequences persisting into adulthood.
Obesity may lead to metabolic complications, such as insulin resistance, which can progress via impaired fasted glucose and impaired glucose tolerance to type 2 diabetes mellitus (T2DM) and to the development of micro- and macro-vascular complications.
Metformin, an oral anti-diabetic licensed for T2DM for adults and children from 10 years onwards, is already used off label in obese children and adolescents with insulin resistance, even though the specific effects of metformin in these obese children and adolescents have not been elucidated, particularly upon long-term use.
The rationale for this study is based on the hypothesis that metformin may reduce body mass index (BMI), insulin resistance and percentage of body-fat in obese children and adolescents with insulin resistance. Further more it is anticipated that metformin may delay the progression to T2DM and thereby micro- and macro-vascular complications in obese children and adolescents with insulin resistance.
Studientyp
Einschreibung (Tatsächlich)
Phase
- Phase 3
Kontakte und Standorte
Studienorte
-
-
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's Hertogenbosch, Niederlande
- Jeroen Bosch Hospital
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Nieuwegein, Niederlande, 3430EM
- St. Antonius Hospital
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-
Teilnahmekriterien
Zulassungskriterien
Studienberechtigtes Alter
Akzeptiert gesunde Freiwillige
Studienberechtigte Geschlechter
Beschreibung
Inclusion Criteria:
- Age ≥ 10 and ≤ 16 years at study entry
- Caucasian descent
- Obesity defined as BMI-SDS > 2.3
- Insulin resistance defined as HOMA-IR ≥ 3.4.
- An obtained informed consent from subjects and parents/caregivers.
Exclusion Criteria:
- Presence of T2DM (American Diabetes Association criteria)
- Presence of endocrine disorders with steroid therapy
- Suspicion of polycystic ovarium syndrome;
- Height < -1.3 SD of target height;
- Syndrome disorders with or without mental retardation;
- Use of anti-hyperglycaemic drugs;
- Pregnancy (pregnancy test will be performed, if applicable);
- (History of) alcohol abuse;
- Impaired renal and/or hepatic function (defined as GFR < 80 ml/min. GFR=40 x length (cm) / serumcreatinin (μmol/l and ALAT >150% of normal value for age);
- Use of ritonavir; use of ACE inhibitors;
- Insufficient knowledge of the Dutch language.
Studienplan
Wie ist die Studie aufgebaut?
Designdetails
- Hauptzweck: Behandlung
- Zuteilung: Zufällig
- Interventionsmodell: Parallele Zuordnung
- Maskierung: Verdreifachen
Waffen und Interventionen
Teilnehmergruppe / Arm |
Intervention / Behandlung |
---|---|
Aktiver Komparator: Metformin
Metformin with lifestyle intervention during 18 months
|
Oral administration, 500 mg daily at week 1.
Every week metformin dosage increases with 500 mg, to a maximum dose of 1000 mg bid.
This maximum dose will be administered till the end of the study.
Andere Namen:
Lifestyle intervention: 18 months physical therapy and dietary advice
|
Placebo-Komparator: Placebo
Placebo and lifestyle intervention during 18 months
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Lifestyle intervention: 18 months physical therapy and dietary advice
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Was misst die Studie?
Primäre Ergebnismessungen
Ergebnis Maßnahme |
Maßnahmenbeschreibung |
Zeitfenster |
---|---|---|
Change in BMI from baseline
Zeitfenster: 18 months and 36 months
|
Change in BMI after part 1 (double blind) and part 2 ( follow-up)
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18 months and 36 months
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Change in Insulin resistance from baseline
Zeitfenster: 3; 6; 9; 12; 15; 18; 24; 30 and 36 months
|
calculated by the Homeostasis Model Assessment for Insulin Resistance (HOMA-IR).
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3; 6; 9; 12; 15; 18; 24; 30 and 36 months
|
Sekundäre Ergebnismessungen
Ergebnis Maßnahme |
Maßnahmenbeschreibung |
Zeitfenster |
---|---|---|
Renal and hepatic function
Zeitfenster: 3; 6; 9; 12; 15; 18; 24; 30 and 36 months
|
creatinine and alat
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3; 6; 9; 12; 15; 18; 24; 30 and 36 months
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Tolerability
Zeitfenster: 3; 6; 9; 12; 15; 18; 24; 30 and 36 months
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The amount of reported adverse effects, in relation to the achieved dose level.
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3; 6; 9; 12; 15; 18; 24; 30 and 36 months
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Pharmacokinetics (PK)-parameters: clearance (ml/min)
Zeitfenster: 9 months
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Clearance where applicable expressed per body weight, age category, Tanner Stage and gender, clearance will be determined with a two-compartment pharmacokinetic model using non linear mixed effect modelling.
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9 months
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Body fat percentage
Zeitfenster: 0, 9, 18 and 36 months
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0, 9, 18 and 36 months
|
|
Physical fitness
Zeitfenster: 0, 9, 18 and 36 months
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0, 9, 18 and 36 months
|
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Quality of life
Zeitfenster: 0, 9, 18 and 36 months
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0, 9, 18 and 36 months
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Long term efficacy
Zeitfenster: 36 months
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Based on BMI and HOMA-IR values
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36 months
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Long-term safety
Zeitfenster: 36 months
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Renal and hepatic function after 36 months of metformin use
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36 months
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Long-term tolerability
Zeitfenster: 36 months
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The amount of adverse effects after 36 months
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36 months
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Microvascular complications
Zeitfenster: 36 months
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Measured as micro-albuminuria
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36 months
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Macrovascular complications
Zeitfenster: 36 monthts
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Measured with Pulse Wave Velocity and Augmentation Index.
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36 monthts
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Development of T2DM
Zeitfenster: 36 months
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36 months
|
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PK-parameters: volume of distribution (liters)
Zeitfenster: 9 months
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Volume of distribution, where applicable expressed per body weight, age category, Tanner Stage and gender, volume of distribution will be determined with a two-compartment pharmacokinetic model using non linear mixed effect modelling.
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9 months
|
Mitarbeiter und Ermittler
Sponsor
Mitarbeiter
Ermittler
- Hauptermittler: Marja MJ van der Vorst, MD, PhD, St. Antonius Hospital
Publikationen und hilfreiche Links
Allgemeine Veröffentlichungen
- van Rongen A, van der Aa MP, Matic M, van Schaik RHN, Deneer VHM, van der Vorst MM, Knibbe CAJ. Increased Metformin Clearance in Overweight and Obese Adolescents: A Pharmacokinetic Substudy of a Randomized Controlled Trial. Paediatr Drugs. 2018 Aug;20(4):365-374. doi: 10.1007/s40272-018-0293-1.
- van der Aa MP, Hoving V, van de Garde EM, de Boer A, Knibbe CA, van der Vorst MM. The Effect of Eighteen-Month Metformin Treatment in Obese Adolescents: Comparison of Results Obtained in Daily Practice with Results from a Clinical Trial. J Obes. 2016;2016:7852648. doi: 10.1155/2016/7852648. Epub 2016 Dec 22.
- van der Aa MP, Elst MA, van Mil EG, Knibbe CA, van der Vorst MM. METFORMIN: an efficacy, safety and pharmacokinetic study on the short-term and long-term use in obese children and adolescents - study protocol of a randomized controlled study. Trials. 2014 Jun 5;15:207. doi: 10.1186/1745-6215-15-207.
Studienaufzeichnungsdaten
Haupttermine studieren
Studienbeginn
Primärer Abschluss (Tatsächlich)
Studienabschluss (Tatsächlich)
Studienanmeldedaten
Zuerst eingereicht
Zuerst eingereicht, das die QC-Kriterien erfüllt hat
Zuerst gepostet (Schätzen)
Studienaufzeichnungsaktualisierungen
Letztes Update gepostet (Tatsächlich)
Letztes eingereichtes Update, das die QC-Kriterien erfüllt
Zuletzt verifiziert
Mehr Informationen
Begriffe im Zusammenhang mit dieser Studie
Schlüsselwörter
Zusätzliche relevante MeSH-Bedingungen
Andere Studien-ID-Nummern
- Metformin 2011-6
- 2010-023980-17 (EudraCT-Nummer)
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